A Phase III Randomized Trial of Dose Escalated Radiation in Locally Advanced Pancreas Cancer (LAPC) Patients (LAP100)
This phase III trial compares the effect of dose-escalated radiation therapy to usual care in patients with locally advanced unresectable pancreatic ductal adenocarcinoma who have received an initial 4-6 months of chemotherapy. Usual care options include additional chemotherapy, observation, or standard lower-dose radiation therapy. These treatments may delay tumor growth but have not been shown to improve survival. Radiation therapy uses high energy X-rays to kill cancer cells and shrink tumors. Dose-escalated radiation therapy involves the precise delivery of higher doses to the tumor, often over a shorter period of time. This trial assesses whether using dose-escalated radiation therapy can prolong survival.
• At time of enrollment, the patient must have received 4-6 months of active chemotherapy with FOLFIRINOX (8-12 cycles) or NALIRIFOX (8-12 cycles) or gemcitabine/nab-paclitaxel (4-6 cycles) (1 regimen, no sequential chemotherapy). Active chemotherapy refers to time on chemotherapy not counting treatment breaks (i.e. if a patient had 1 month of chemotherapy followed by 1 month break, this would count as 1 month chemotherapy). Study registration must occur within 45 days of last day of chemotherapy cycle
• BASELINE PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
• Pathologically (histologically or cytologically) proven diagnosis of pancreatic ductal adenocarcinoma
• Locally advanced unresectable disease (as defined per the National Comprehensive Cancer Network \[NCCN\] guidelines and institutional tumor board review)
• Patients must have baseline pre-chemotherapy scans for staging. Options include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment
• Age ≥ 18 years
• Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
• Baseline CA19-9 with a normal bilirubin level (defined as ≤ 1.2 mg/dl)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN)
• POST PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
• If baseline CA19-9 is elevated (defined as \> 37 u/mL) the post-pre-entry chemotherapy CA19-9 must be less than 37 u/mL or a 50% decline from pre-chemotherapy level with absolute value less than 100u/mL
• If baseline CA19-9 is not elevated (defined as ≤ 37 u/mL) the post-pre-entry chemotherapy CA19-9 must remain ≤ 37 u/mL
• No active duodenal or gastric ulcers
• No direct tumor invasion of the bowel or stomach
• Restaging scans showing at least stable disease (no progression). Options for scans include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment, with restaging CT showing at least stable disease
• Not pregnant and not nursing
• No cardiac condition that was the primary reason for hospitalization in the last 6 months
• New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial